1. Lyso-SM-509 is a highly specific and sensitive biomarker for the identification of Niemann-Pick patients: a 30 months study

Lyso-SM-509 is a highly specific and sensitive biomarker for the identification of Niemann-Pick patients: a 30 months study

Claudia Cozma, MD 1 Prof. Peter Bauer, MD 1 Gabriela-Elena Oprea, PhD 1 Jan Lukas, PhD 2 Susanne Zielke 2 Prof. Arndt Rolfs, MD 1, 2
1 CENTOGENE AG 2 University of Rostock
September 26, 2017

Introduction

Niemann Pick Type C (NPC) disease is an autosomal recessive disease caused by mutations in NPC1 or NPC2 genes translated in defects of the lysosomes cholesterol transport system leading to abnormal accumulation of cholesterol and glycolipids in the lysosome. Recently developed treatment renders early NPC diagnosis of high most importance.

Material and Methods:

We present data from a 2 year global cohort of Niemann Pick patients using lyso-SM-509 biomarker determination, followed by sequencing of NPC1/2 genes. Determination of lyso-SM-509 is performed by LC/MRM-MS in plasma, serum, EDTA blood anddried blood spots (DBS). We identified in a world-wide study using lyso-SM-509 as primary screening in DBS samples 313 NPC affected patients. The diagnosis was confirmed by sequencing of the NPC1/NPC2 by single gene sequencing, NGS, or MLPA. In NPC1/2 sequencing negative patients with increased lyso-SM-509 concentrations the sequencing of sphingomyelinase (SMPD1) gene was done. We could identify over 807 pathological alleles in 488 different individuals.

Summary:

The levels of lyso-SM-509 in blood has a sensitivity of 100 % and specificity of 99.15 % for NPC1/2 and it reflects the burden of the NP disease and it can be used for the easy diagnosis of NPC patients and for the monitoring of the disease progression.

These findings were presented at the 13th International Congress Inborn Errors of Metabolism (ICIEM 2017).